Transglutaminase 2 is an enzyme that cross-links proteins inside cells and contributes to cellular adhesion in tissues. Our group is interested in its many roles that can tip the balance between cellular proliferation and cell death. Our group’s research projects are currently investigating:
1. Whether the increased presence of TG2 in human breast cancers confers direct effects on survival of breast cancer patients.
2. Whether by reducing the levels of TG2 in cancer cells that have become resistant to anti-cancer drugs we can improve the efficiency of these anti-cancer drugs.
3. Whether natural compounds derived from, e.g., spices and red wine can be used to modulate the levels of TG2 and so modulate the behaviour of breast, kidney, liver and other cancer cells. This research offers the possibility of developing new diagnostic approaches and TG2-based therapies for the treatment of human cancers.
4. New potential roles for cancer cell derived exosomes in chemotherapeutic resistance.
The current work involves a wide range of molecular and biophysical techniques including: immunohistological analysis of transglutaminase 2 in human breast cancer biopsy samples; tissue culture of human cancer cell lines; analysis of TG2 expression in response to drug therapy by cell toxicology assay, membrane purification and analysis, Western blot analysis, confocal microscopy and flow cytometry; RT-PCR analysis of mRNA, SiRNA (silencing) knockdown of mRNA; inductively coupled plasma atomic emission spectroscopy for measurement of cellular uptake of platinum based drugs.
Other specialist biophysical methodologies will be developed as part of these projects – particularly project 4.
Expected outcomes are:
1. Validation of transglutaminase 2 as a biomarker for the progression of tumour progression and patient survival, particularly in breast cancer.
2. Validation of transglutaminase 2 as a drug target in diverse cancers including: liver, breast, prostate and kidney cancers.